TY - JOUR
T1 - Oleate-induced aggregation of LC3 at the trans-Golgi network is linked to a protein trafficking blockade
AU - Cerrato, Giulia
AU - Leduc, Marion
AU - Müller, Kevin
AU - Liu, Peng
AU - Zhao, Liwei
AU - Humeau, Juliette
AU - Xie, Wei
AU - Zhang, Shuai
AU - Kepp, Oliver
AU - Sauvat, Allan
AU - Kroemer, Guido
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Oleate, the most abundant endogenous and dietary cis-unsaturated fatty acid, has the atypical property to cause the redistribution of microtubule-associated proteins 1A/1B light chain 3B (referred to as LC3) to the trans-Golgi network (TGN), as shown here. A genome-wide screen identified multiple, mostly Golgi transport-related genes specifically involved in the oleate-induced relocation of LC3 to the Golgi apparatus. Follow-up analyses revealed that oleate also caused the retention of secreted proteins in the TGN, as determined in two assays in which the secretion of proteins was synchronized, (i) an assay involving a thermosensitive vesicular stomatitis virus G (VSVG) protein that is retained in the endoplasmic reticulum (ER) until the temperature is lowered, and (ii) an isothermic assay involving the reversible retention of the protein of interest in the ER lumen and that was used both in vitro and in vivo. A pharmacological screen searching for agents that induce LC3 aggregation at the Golgi apparatus led to the identification of “oleate mimetics” that share the capacity to block conventional protein secretion. In conclusion, oleate represents a class of molecules that act on the Golgi apparatus to cause the recruitment of LC3 and to stall protein secretion.
AB - Oleate, the most abundant endogenous and dietary cis-unsaturated fatty acid, has the atypical property to cause the redistribution of microtubule-associated proteins 1A/1B light chain 3B (referred to as LC3) to the trans-Golgi network (TGN), as shown here. A genome-wide screen identified multiple, mostly Golgi transport-related genes specifically involved in the oleate-induced relocation of LC3 to the Golgi apparatus. Follow-up analyses revealed that oleate also caused the retention of secreted proteins in the TGN, as determined in two assays in which the secretion of proteins was synchronized, (i) an assay involving a thermosensitive vesicular stomatitis virus G (VSVG) protein that is retained in the endoplasmic reticulum (ER) until the temperature is lowered, and (ii) an isothermic assay involving the reversible retention of the protein of interest in the ER lumen and that was used both in vitro and in vivo. A pharmacological screen searching for agents that induce LC3 aggregation at the Golgi apparatus led to the identification of “oleate mimetics” that share the capacity to block conventional protein secretion. In conclusion, oleate represents a class of molecules that act on the Golgi apparatus to cause the recruitment of LC3 and to stall protein secretion.
UR - http://www.scopus.com/inward/record.url?scp=85097679901&partnerID=8YFLogxK
U2 - 10.1038/s41418-020-00699-3
DO - 10.1038/s41418-020-00699-3
M3 - Article
C2 - 33335289
AN - SCOPUS:85097679901
SN - 1350-9047
VL - 28
SP - 1733
EP - 1752
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 5
ER -